Remedial Dosing Recommendations for Sirolimus Delayed or Missed Dosages Caused by Poor Medication Compliance in Pediatric Tuberous Sclerosis Complex Patients


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Abstract

Background::Delayed or missed dosages caused by poor medication compliance significantly affected the treatment of diseases in children.

Aims::The present study aimed to investigate the influence of delayed or missed dosages on sirolimus pharmacokinetics (PK) in pediatric tuberous sclerosis complex (TSC) patients and to recommend remedial dosages for nonadherent patients.

Methods::A published sirolimus population PK model in pediatric TSC patients was used to assess the influence of different nonadherence scenarios and recommend optimally remedial dosages based on Monte Carlo simulation. Thirteen nonadherent scenarios were simulated in this study, including delayed 2h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 16 h, 18 h, 20 h, 22 h, 23.5 h, and missed one dosage. Remedial dosing strategies contained 10-200% of scheduled dosages. The optimal remedial dosage was that with the maximum probability of returning the individual therapeutic range.

Results::For delayed or missed sirolimus dosages in pediatric TSC patients, when the delayed time was 0-8 h, 8-10 h, 10-18 h, 18-22.7 h, 22.7-24 h, 70%, 60%, 40%, 30%, 20% scheduled dosages were recommended to take immediately. When one dosage was missed, 120% of scheduled dosages were recommended at the next dose.

Conclusion::It was the first time to recommend remedial dosages for delayed or missed sirolimus therapy caused by poor medication compliance in pediatric TSC patients based on Monte Carlo simulation. Meanwhile, the present study provided a potential solution for delayed or missed dosages in clinical practice.

About the authors

Yang Yang

Department of Pharmacy, The Affiliated Changzhou Children’s Hospital of Nantong University

Email: info@benthamscience.net

Lei Jiang

Department of Pharmacy, Taixing People's Hospital

Email: info@benthamscience.net

Hai-Rong Zhu

School of Nursing, Xuzhou Medical University

Email: info@benthamscience.net

Wen-Xin Sun

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University

Email: info@benthamscience.net

Jing-Yu Mao

School of Nursing, Xuzhou Medical University

Email: info@benthamscience.net

Jing-Wen Miao

School of Nursing, Xuzhou Medical University

Email: info@benthamscience.net

Yi-Chen Wang

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University

Email: info@benthamscience.net

Su-Mei He

Department of Pharmacy, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University

Author for correspondence.
Email: info@benthamscience.net

Dong-Dong Wang

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy,, Xuzhou Medical University

Author for correspondence.
Email: info@benthamscience.net

Xiao Chen

School of Nursing, Xuzhou Medical University

Author for correspondence.
Email: info@benthamscience.net

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